Electroporation-Based Biopsy Treatment Planning with Numerical Models and Tissue Phantoms.

Molecular sampling with vacuum-assisted tissue electroporation is a novel, minimally invasive method for molecular profiling of solid lesions. In this paper, we report on the design of the battery-powered pulsed electric field generator and electrode configuration for an electroporation-based molecular sampling device for skin cancer diagnostics. Using numerical models of skin electroporation corroborated by the potato tissue phantom model, we show that the electroporated tissue volume, which is the maximum volume for biomarker sampling, strongly depends on the electrode's geometry, needle electrode skin penetration depths, and the applied pulsed electric field protocol. In addition, using excised human basal cell carcinoma (BCC) tissues, we show that diffusion of proteins out of human BCC tissues into water strongly depends on the strength of the applied electric field and on the time after the field application. The developed numerical simulations, confirmed by experiments in potato tissue phantoms and excised human cancer lesions, provide essential tools for the development of electroporation-based molecular markers sampling devices for personalized skin cancer diagnostics.

Treating scars after burns with pulsed electric fields in the rat model.

Reducing scar size after severe burn injuries is an important and challenging medical, technology and social problem. We have developed a battery-powered pulsed electric field (PEF) device and surface needle electrode applicator to deliver pulsed electric fields to the healing dorsal burn wound in rats. PEF was used to treat residual burn wounds caused by metal contact in rats starting 10 days after the injury for 4 months every 11 or 22 days for 4 months using varying time applied voltages at 250-350V range, 400mA current, 40 pulses, 70 µs duration each, delivered at pulse repetition frequency 10 Hz at 5 locations inside the wound. We found 40-45% reduction in the scar size in comparison with untreated controls in both upper and lower dorsal locations on rats' backs two months after the last PEF application. We have not detected significant histopathological differences in the center of the scars besides the thickness of the newly generated epidermis, which was thicker in the PEF treated group.We showed that minimally invasively applied pulsed electric fields through needle electrodes are effective method and device for treating residual burn wounds in the rat model, reducing the size of the resulting scars, without any adverse reaction.

Electroporation-based proteome sampling ex vivo enables the detection of brain melanoma protein signatures in a location proximate to visible tumor margins.

A major concern in tissue biopsies with a needle is missing the most lethal clone of a tumor, leading to a false negative result. This concern is well justified, since needle-based biopsies gather tissue information limited to needle size. In this work, we show that molecular harvesting with electroporation, e-biopsy, could increase the sampled tissue volume in comparison to tissue sampling by a needle alone. Suggested by numerical models of electric fields distribution, the increased sampled volume is achieved by electroporation-driven permeabilization of cellular membranes in the tissue around the sampling needle. We show that proteomic profiles, sampled by e-biopsy from the brain tissue, ex vivo, at 0.5mm distance outside the visible margins of mice brain melanoma metastasis, have protein patterns similar to melanoma tumor center and different from the healthy brain tissue. In addition, we show that e-biopsy probed proteome signature differentiates between melanoma tumor center and healthy brain in mice. This study suggests that e-biopsy could provide a novel tool for a minimally invasive sampling of molecules in tissue in larger volumes than achieved with traditional needle biopsies.